The pathogenesis of the anemia of chronic disease is not understood. A recently identified peptide, hepcidin, has been found to be aberrantly expressed in hepatic adenomas in GSD (GSD), resulting in an iron-resistant iron-deficiency anemia similar to that seen in the anemia of chronic disease. Hepcidin is postulated to be involved in the pathogenesis of the anemia of chronic disease, and these investigations are aimed at characterizing the role of hepcidin in both normal iron homeostasis and in subjects with the anemia of chronic disease. The specific aims are the following: 1) To evaluate the relationship between adenoma tumor burden and anemia; 2) To characterize iron absorption and distribution in normal controls, anemic patients, and patients with GSD Type 1 at (GSD1a; 3) To compare hepcidin expression in normal individuals and patients with GSD1a, and 4) To determine the role of hepcidin as a mediator of the anemia of chronic disease in patients with other inflammatory conditions. Methodology: The relationship between iron homeostasis and hepcidin expression will be studied in normal and pathologic states including GSD1a, juvenile rheumatoid arthritis, and inflammatory bowel disease. As inappropriate hepcidin expression has been demonstrated in hepatic adenomas in patients with GSD, direct observational studies in this population will be performed to allow further clinical correlation between these lesions and indices of erythropoiesis and iron status. Oral absorption of iron will be investigated in all subjects to define the relationship between hepcidin and iron absorption. For the inflammatory disorders, the oral iron challenge tests and direct measurement of hepcidin will be performed during periods of disease remission and exacerbation. The relationship between hepcidin and inflammatory markers will also be investigated. Through these studies, the role of hepcidin as a mediator of anemia of chronic disease will be elucidated. Improved understanding of the pathophysiology of the anemia of chronic disease will lay the foundation for new treatments for anemia and disorders of iron homeostasis.